Cancer and immunology interest remains strong even as firms try to diversify.

De-risking and tightening the focus were the operative words for many of the companies in San Francisco for the 30th Annual J.P. Morgan Healthcare Conference the week of January 9. Although the focus on oncology is unabated, many companies are addressing orphan diseases and unmet needs. Interest in immunotherapy was strong, with various firms discussing varied approaches to solve previously intractable problems.

Highlights from GEN’s Week in San Francisco

Aegerion Pharmaceuticals built out its global management team in 2011 and is focused on executing its strategy for orphan and ultra-orphan diseases this year. Its lead compound targets homozygous familial hypercholesterolemia (HoFH), in which LDC levels measure 500 to 1,000 mg. “Thirty-five percent ended the trial with LDL-c levels below 100,” Marc D. Beer, CEO, says. “We expect to file in the U.S. and EU this quarter and are asking for priority review and single cycle approval.”

Ariel Pharmaceuticals focuses on in-licensing drugs that are ready for the clinic and have well-defined endpoints. “De-risking is part of our original strategy,” Steve Orndorff, Ph.D., CEO, tells GEN. The company is advancing therapies for migraine, hemorrhagic shock, and traumatic brain injury. “Our lead candidate for acute migraine is in Phase II clinical studies.”

Unlike the onslaught of generic triptan and derivative therapies that are bombarding physicians, AP1531 is a novel EP4 receptor antagonist with a dual mechanism of action to regulate the release of neuropeptides and vasoconstrictors. For 2012, Dr. Orndorff predicts more competition for grants but more generous awards. “We are applying for several new U.K. and EU grants through our London office,” as well as U.S. grants.

Celldex Therapeutics develops immune therapies “focused on antibody drug conjugates, vaccines, and therapeutic proteins, and we’re moving into late-stage development for a Phase III trial for brain cancer,” Anthony Marucci, president and CEO, told GEN. Four oncology drugs are in Phase I, II, and III development. The most advanced, rindopepimut, is being evaluated as a treatment for EGFR positive glioblastoma.

Additionally, enrollment is about to be completed for CDX-011, a mAb drug conjugate for metastatic breast cancer, with Phase II results expected in the first half of the year. CDX-1127, an anti-CD27 mAb, is being studied in hematologic cancers, and CDX-1401 is a fusion protein of a fully human mAb that is specific for the dendritic cell receptor. It has application in a wide variety of cancers. Both the CDX-1401 and CDX-1127 are in Phase I trials. “These are targeted therapies, but they are not patient-specific,” Marucci explained.

Emergent BioSolutions has $2.5 billion in products sold or under contract since 2004, according to Daniel J. Abdun-Nabi, president and CEO, speaking at the J.P. Morgan conference. The company is interested in autoimmune and infectious diseases and oncology and has a history of acquiring advanced stage clinical programs. “Acquisitions are key,” Abdun-Nabi stressed. The company’s two divisions are organized around biodefense and biosciences. BioThrax® is the only FDA-licensed anthrax vaccine.

“We’re looking to evergreen BioThrax, extend the shelf life to five years, and expand manufacturing capacity from 7 to 9 million doses per year to 24 million doses per year.” The new building was designed with that objective and includes the capacity to double production to 50 million doses per year. The goal is to produce the 75 million dose stockpile the U.S. government requires. “Several products are in the pipeline to address the anthrax threat, including Anthrivig™, reviThrax, and NuThrax,” Abdun-Nabi added.

Geron is divesting its stem cell business and focusing on oncology products, with emphasis on two candidates and unmet needs, according to John A. Scarlett, M.D., president and CEO. “We expect top-line results this year, with broad patent protection through 2025 for both programs. Imetelstat is the only clinical-stage telomerase inhibitor. This is only transiently expressed in normal tissues but is up-regulated in approximately 90 percent of human tumor biopsies.”

After tumor de-bulking, imetelstat holds the promise of inhibiting tumor growth in a wide variety of tumor types. Geron’s Phase I, 183-patient program shows telomerase inhibition of more than 50% in tissue. Phase II trials are under way for metastatic breast cancer and for non-small-cell lung cancer. The therapy is being considered for maintenance after the chemotherapy. Geron also is developing Geron 1005 against brain tumors, using the LRP-1 receptors to transport large molecules across the blood brain barrier. Results from two single-arm studies are expected in the second quarter of 2013.

Idera Pharmaceuticals is developing compounds targeted to toll-like receptors to treat oncology as well as respiratory, infectious, inflammatory, and autoimmune diseases. Sudhir Agrawal, D.Phil, chairman and CEO, told GEN, “IMO-2055, the lead candidate, induces both the innate and adaptive immune response, triggering a very strong antitumor activity.” Results from lung and colon cancer Phase I trials are expected in the first and second quarter of 2012, and additional studies are under way for other indications.

ImmunoGen plans to build its pipeline rapidly in 2012, both on its own and through partnerships that enhance cash flow and enhance knowledge, said Daniel Junius, president and CEO, reporting at the J.P. Morgan conference. He bills T-DM1 as the successor to Herceptin®. In development with Roche, Phase III data is expected later this year. Immunogen’s proprietary pipeline features IMGN-901, a CD56+ first-line small cell lung cancer therapeutic. “It has been 25 years since a new therapy has been introduced for that disease. Merkel cell carcinoma also will benefit,” Junius said.

Immunovaccine is advancing its DepoVax™ adjuvant technology platform against solid tumor cancers, hepatitis B, pandemic flu, and anthrax, John Trizzino, CEO, told GEN. “DPX-0907 just completed Phase I trials, and DPX-Survivac began patient enrollment for Phase I trials with approved protocols for Phase I and II trials from the FDA and from Health Canada. It generates 10 to 20 times more robust and durable immune response.”

Immunovaccine’s immunotherapeutic approach encapsulates the antigen and adjuvant in a liposome that is lyophilized, reconstituted in an oil, and then injected subcutaneously. This attracts immune cells to the site to generate humoral and/or cellular responses. It is administered after tumor removal and chemotherapy. “We have broad patent protection through 2021 and pending patents to extend protection to 2028 and 2031.”

Oncothyreon is developing late-stage cancer vaccines in the immunotherapy and small molecular spaces. “The immunotherapy work is internal, the small molecular work was in-licensed or acquired,” Robert Kirkman, M.D., CEO, explained to GEN. “The most advanced candidate is a therapeutic called Stimuvax, being developed with Merck KGaA. It’s in a 1,500-patient global Phase II trial for non-small-cell lung cancer that will end later this year.”

An earlier trial showed a 17-month survival advantage for those who received the vaccine. The target, MUC1, is widely present on several types of tumor cells. “We combine a 25 amino acid peptide with an adjuvant and three fats, creating a liposome that expresses antigen and adjuvant on its surface. This is injected subcutaneously to trigger an immune response,” he elaborates. Oncothyreon also is developing another vaccine entirely in-house, using a larger antigen to generate a T-cell response. “Our internal efforts are focused on the small molecule inhibitors PI3 kinase alone and in combination with other agents.

PsiOxus plans to complete its 50-patient, Phase II trial for cachexia, the wasting disease of cancer, this quarter. “The compound is a small molecule, catabolic anabolic transforming agent that stops tissue breakdown and promotes tissue buildup,” John Beadle, M.D., CEO, told GEN. The second major program, for oncolytic virus, is beginning Phase I trials, targeting colorectal cancer. The company is using a chimeric virus that doesn’t exist in nature and was developed using the principles of evolution. “The virus kills cancer cells but not normal cells,” Beadle noted. “It is very potent against a wide range of cancers and is stable in human blood so it can be delivered intravenously. Once at the tumor site, it amplifies, killing the tumor.”

Spectrum Pharmaceuticals’ Rajest Shrotiriya, M.D., chairman, president, and CEO developed the company around in-licensing late-stage drugs. “By having no drug discovery, we eliminate many of the risks. We let the world be our laboratory,” he told the crowd at the J.P. Morgan conference. European studies show Zevalin® completely transforms lymphoma treatments to an injection of rituximab at week one, another at week two, and then an injection of Zevalin.

No other therapy is required for eight years, he emphasized. Overall response rate is 83%. Spectrum has filed an NDA for Zevalin. The company is growing the market for Fusilev® for colorectal cancer and expects to file an NDA later this year for Apaziquone in noninvasive bladder cancer.

Tocagen is developing a breakthrough therapeutic platform for brain cancer that selectively targets a retrovirus that grows on tumors. Consequently, it has the potential to eradicate the tendrils of tumors that remain in the brain after resection. As Harry E. Gruber, M.D., CEO, told GEN, “this virus is engineered to carry a gene that expresses an enzyme not found in humans. When it expresses in the cancer cell, it does nothing until the patient is given the drug 5-FC. The 5-FC then converts into 5-FU, an extremely toxic anticancer agent. One hundred times more 5-FU is created in the tumor than could be safely given intravenously, but its half-life is only one minute. It’s enough to kill the tumor.”